I plan to study the pathophysiology and biochemical events associated with the transition from fetal hemoglobin synthesis to adult hemoglobin synthesis. Particular attention will be paid to those aspects of the problem in which the pathogenesis of the persistence of fetal hemoglobin can be explained. In addition to being a uniquely useful model system in which one can study the differentiation of well characterized proteins in vertebrates, the hemoglobin transition is also involved in several clinically significant disease states in which fetal hemoglobins are found in adults. We hope to develop a cell-free system for the synthesis of human fetal hemoglobin in order to test several possible control mechanisms which could regulate hemoglobin synthesis at the translational level.